PET measures of benzodiazepine receptors in progressive supranuclear palsy

Objective: To evaluate the integrity of neurons containing benzodiazepine r eceptors in metabolically affected regions of the brain in patients with cl inically diagnosed progressive supranuclear palsy (PSP). Methods: The cereb ral distribution of [C-11]flumazenil (FMZ), a ligand that binds to the gamm a-aminobutyric acid A (GABA(A)) receptor, and [F-18]fluorodeoxyglucose (FDG ), a measure of local cerebral glucose metabolism, was determined with PET in 12 patients with PSP and 10 normal control subjects. Tracer kinetic anal ysis was applied to quantify data and analysis was performed using three-di mensional stereotactic surface projections and stereotactically determined volumes of interest. Results: There was a global reduction in FMZ binding o f 13%, with a reduction in the anterior cingulate gyrus of 20% (p = 0.004), where glucose metabolic rates also showed the greatest reduction. Conclusi ons: PSP causes loss of benzodiazepine receptors in the cerebral cortex. Co nsistent with postmortem studies, the authors did not find significant chan ges in FMZ binding in subcortical nuclei that exhibit the most pathologic c hange. This study suggests that both loss of intrinsic neurons containing b enzodiazepine receptors and deafferentation of the cerebral cortex from dis tant brain regions contribute to cerebral cortical hypometabolism in PSP.